We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Cancer in Inherited Bone Marrow Failure Syndromes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00027274
Recruitment Status : Recruiting
First Posted : November 30, 2001
Last Update Posted : December 20, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:


A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders.

Mutations in IBMFS genes are relevant to carcinogenesis in sporadic cancers.

Patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer.

These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer.

Carriers of IBMFS gene mutations are at increased risk of cancer.

The prototype disorder is Fanconi's Anemia (FA); other IBMFS will also be studied.


To determine the types and incidence of specific cancers in patients with an IBMFS.

To investigate the relevance of IBMFS gene mutations in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers.

To identify risk factors for IBMFS-related cancers in addition to the primary germline mutations.

To determine the risk of cancer in IBMFS carriers.


North American families with a proband with an IBMFS.

IBMFS suspected by phenotype, confirmed by mutation in an IBMFS gene, or by clinical diagnostic test.

Fanconi's anemia: birth defects, marrow failure, early onset malignancy; positive chromosome breakage result.

Diamond-Blackfan anemia: pure red cell aplasia; elevated red cell adenosine deaminase.

Dyskeratosis congenita: dysplastic nails, lacey pigmentation, leukoplakia; marrow failure.

Shwachman-Diamond Syndrome: malabsorption; neutropenia.

Amegakaryocytic thrombocytopenia: early onset thrombocytopenia.

Thrombocytopenia absent radii: absent radii; early onset thrombocytopenia.

Severe Congenital Neutropenia: neutropenia, pyogenic infections, bone marrow maturation arrest.

Pearson's Syndrome: malabsorption, neutropenia, marrow failure, metabolic acidosis; ringed sideroblasts.

Other bone marrow failure syndromes: e.g. Revesz Syndrome, WT, IVIC, radio-ulnar synostosis, ataxia-pancytopenia.

First degree relatives of IBMFS-affected subjects as defined here, i.e. siblings (half or full), biologic parents, and children.

Grandparents of IBMFS-affected subjects.

Patients in the general population with sporadic tumors of the types seen in the IBMFS (head and neck, gastrointestinal, and anogenital cancer), with none of the usual risk factors (e.g. smoking, drinking, HPV).


Natural history study, with questionnaires, clinical evaluations, clinical and research laboratory test, review of medical records, cancer surveillance.

Primary endpoints are all cancers, solid tumors, and cancers specific to each type of IBMFS.

Secondary endpoints are markers of pre-malignant conditions, such as leukoplakia, serum or tissue evidence of carcinogenic viruses, and bone marrow morphologic myelodyplastic syndrome or cytogenetic clones..

Condition or disease
Aplastic Anemia Head and Neck Neoplasms Bone Marrow Failure

  Show Detailed Description

Study Design

Study Type : Observational
Estimated Enrollment : 4000 participants
Observational Model: Family-Based
Time Perspective: Other
Official Title: Etiologic Investigation of Cancer Susceptibility in Inherited Bone Marrow Failure Syndromes: A Natural History Study
Study Start Date : January 1, 2002

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :
  1. Cohort of Families with IBMFS [ Time Frame: Ongoing ]
    Establish a cohort of families with IBMFS

  2. Biology of Patients Compared with Healthy Controls [ Time Frame: Ongoing ]
    Compare biology of IBMFS patients with general populations

  3. Differences Between Patients and Healthy Controls [ Time Frame: Ongoing ]
    Identify differences between patients with IBMFS who develop cancer and those who don't

  4. Risk of Cancer with Specific Mutations [ Time Frame: Ongoing ]
    Determine risk of cancer in IBMFS patients with specific gene mutations

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   up to 120 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
  • Fanconi s anemia.
  • Diamond Blackfan anemia.
  • Dyskeratosis congenita.
  • Shwachman Diamond Syndrome.
  • Amegakaryocytic thrombocytopenia.
  • Thrombocytopenia absent radii.
  • Severe congenital neutropenia.
  • Pearson s Syndrome.
  • Other bone marrow failure syndromes.
  • First degree relatives of IBMFS-affected subjects as defined here, i.e. siblings (half or full), biologic parents, and children.
  • Grandparents of IBMFS-affected subjects, specifically for Hypothesis 4.
  • Patients in the general population with sporadic tumors of the types seen in the IBMFS (head and neck, gastrointestinal, and anogenital cancer), with none of the usual risk factors for those tumors (e.g. smoking, drinking, HPV).
  • Adult patients and family members who are unable to provide consent.


  • Evidence that the hematologic disorder is acquired rather than genetic. Such evidence includes temporal relation of the aplastic anemia to known marrow suppressant drugs, chemicals, toxins, or viruses (in the absence of evidence indicative of an inherited marrow failure disorder).
  • Known causes of cytopenias such as autoantibodies to red cells, platelets, or neutrophils, viruses (especially hepatitis), micronutrient deficiencies, transient erythroblastopenia of childhood, and cyclic neutropenia.
  • Assignment of the patient s physical findings to other syndromes or causes that are not part of the IBMFS disease spectrum.
  • Unwillingness to permit access to medical records and pathology specimens.

There are no other exclusion parameters not related to the primary disease.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00027274

Contact: Blanche P Alter, M.D. (240) 276-7239 alterb@mail.nih.gov

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Blanche P Alter, M.D. National Cancer Institute (NCI)
More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00027274     History of Changes
Obsolete Identifiers: NCT00056121
Other Study ID Numbers: 020052
First Posted: November 30, 2001    Key Record Dates
Last Update Posted: December 20, 2017
Last Verified: December 17, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Fanconi's Anemia
Diamond Blackfan Anemia
Dyskeratosis Congenita
Shwachman-Diamond Syndrome
Bone Marrow
Inherited Bone Marrow Failure Syndromes
Familial Cancer

Additional relevant MeSH terms:
Anemia, Aplastic
Head and Neck Neoplasms
Hemoglobinuria, Paroxysmal
Pathologic Processes
Hematologic Diseases
Bone Marrow Diseases
Neoplasms by Site
Anemia, Hemolytic
Myelodysplastic Syndromes